A Critical Link between Chronic Stress and Aging

You may know that chronic stress is bad for your health, but a widely publicized study now tells us it could take a decade or more off your life. The study found that chronic psychological stress effectively shaved the equivalent of 9 to 17 years off the length of telomeres, the structures at the tips of chromosomes that serve as a yardstick of biological age. The report, published in Proceedings of the National Academy of Sciences in November, is the first to show a direct link between chronic stress and aging, and it hints of a possible biological mechanism for how stress can shorten lifespan.

The researchers, led by University of California, San Francisco clinical psychologist Elissa S. Epel and molecular biologist Elisabeth H. Blackburn, studied 39 mothers who were caring for a chronically ill child and compared them with 19 mothers of healthy children. They measured the length of telomeres in samples of the women’s white blood cells, which play critical roles in immune function, and assessed the levels of telomerase, an enzyme that can extend shortened telomeres. They also looked at cellular indicators of oxidative damage, a sort of “biological rusting” caused by free radicals that has been linked to aging and age-related diseases.

The researchers found that women who were more stressed, as measured both objectively (years spent caregiving) and subjectively (self-perceived stress levels), had shorter telomeres, lower levels of telomerase, and higher oxidative load. “We saw a clear association between the number of years of caregiving and the excessive telomere shortening and excessive loss of telomerase activity,” says Blackburn. “It looks pretty much like cause and effect—that it’s the stressful situation that is driving those read-outs in the cell.”

“This is a provocative finding in the best sense of the word,” said Stanford University stress expert Robert Sapolsky in a commentary published in Proceedings of the National Academy of Sciences. If the finding can be replicated and generalized to other populations, he wrote, it may ultimately “reveal a detailed pathway by which stress can influence a fundamental aspect of the aging process.”

Telomeres and telomerase have become the focus of intense study in aging research, a sort of fountain of youth at the most fundamental biological level. Each time a cell divides, its telomeres shorten a bit. At a certain threshold, the cell can no longer divide and begins to deteriorate. As cell populations throughout the body deteriorate, the physical effects of aging become apparent: hair turns gray, skin wrinkles, joints and bones weaken, organ systems begin to fail, and cognitive deficits appear.

Numerous scientific reports have documented the progressive shortening of telomeres with age, and at least one study has shown that shorter telomeres are associated with all causes of death in the elderly.

Blackburn cautions that the initial finding, from a small though well-controlled group of subjects, does not

prove a mechanistic pathway from stress to increased oxidative damage to lower telomerase to shortened telomeres. “All we have are observations, clinically and in the lab—sets of numbers that all point to danger signals based on everything we know from previous studies of cells in the lab,” she says. “But we can’t say who’s pushing what.”

Nonetheless, the study has created a stir in the aging-research community. Caleb E. Finch, an expert on genomic regulation of aging at the University of Southern California, calls it “a pioneering investigation” that “opens the door to a new set of processes in human health.”

Researchers are now working to nail down the precise mechanisms by which stress leads to premature aging.

Blackburn, Epel, and their colleagues are now working to nail down the precise mechanisms by which stress leads to premature aging, and to try to generalize the findings to other populations and cell types. They have initiated studies to look at telomere length and telomerase activity in people with depression and in people who are undergoing stress-intervention programs. They want to know, for example, how yoga, meditation, or other proven stress-management techniques might impact these cellular measures of aging.

“We don’t know yet if this finding generalizes at all,” Blackburn said. “We have no reason to think it doesn’t, but until you ask the question, you can only guess.”